- Water (e.g. ad libitum): test substance was administered in water, which was available ad libitum. Water consumption was measured in the first and second weeks, and then every two weeks, to obtain an average daily dose and a cumulative dose.

- Dose selection rationale: The dose used was chosen on the assumption that a certain amount (10%) can be swallowed by using a tooth-paste containing 0.5 -1% HEDP.

- Rationale for animal assignment (if not random): no information

Details on dosing and sampling:

PHARMACOKINETIC STUDY ( distribution)

- Tissues and body fluids sampled: blood, tibia

- Time and frequency of sampling: every four weeks in four test animals and two control animals.

- Radioactivity of organs was determined after drying.

- X-rays were taken to determine distribution of radiation, and morphology of bones.

- Other: Test animals remaining after 106 weeks treatment were observed for another 33 weeks, and then killed. Necroscopies were carried out.

Statistics:

t-test for water and food consumption, U-test for organ weight.

Results and discussion

Main ADME results

Type:

distribution

Results:

small amount of test substance found in bones 0.033% in total skeleton; 0.0065% after test period

Toxicokinetic / pharmacokinetic studies

Details on absorption:

After 4 weeks 0.069 mg HEDP/kg bone (1.1 µg absolute) was found in the skeleton. This is equivalent to 0.033% of the substance administered. After 104 weeks the amount in the skeleton was 0.0065% of the overall intake. As the radioactive levels of all organs and tissue samples with the exception of bone and intestine were only slightly above the limit of detection, the amount of HEPD absorbed from drinking water was apparently low.

Details on distribution in tissues:

Very little radioactivity was detected anywhere except in the bones. About 95% of the absorbed HEDP was found in the skeleton and 3% in the liver.

Details on excretion:

not specified

Metabolite characterisation studies

Metabolites identified:

not specified

Details on metabolites:

not specified

Any other information on results incl. tables

X ray studies showed that there was no influence of HEDP on morphology and length of bones.

Food consumption and body weight increased slightly in comparison with the control group.

No treatment related effects were observed in the following evaluations:

Table 1 Distribution of ¹⁴C after 2 year exposure to 3.3 ppm¹⁴C-HEDP in drinking water

Organ

¹⁴C-activity in % overall intake

¹⁴C-activity, relative distribution (%)

Intestine

5.7 ± 5.4 x 10ˉ³

40.70

Bones

7.6 ± 1.2 x 10ˉ³

54.30

Thyroid gland

1.3 ± 0.2 x 10ˉ⁵

0.09

Stomach

1.0 ± 0.7 x 10ˉ⁴

0.71

Bladder

4.2 ± 1.2 x 10ˉ⁵

0.30

Liver

2.6 ± 1.1 x 10ˉ⁴

1.86

Lungs

2.1 ± 0.5 x 10ˉ⁵

0.15

Tongue

4.7 ± 4.7 x 10ˉ⁶

0.03

Kidneys

3.1 ± 0.1 x 10ˉ⁵

0.22

Testicles

4.0 ± 1.7 x 10ˉ⁵

0.28

Eyes

2.8 ± 1.9 x 10ˉ⁶

0.02

Muscles

2.2 ± 0.5 x 10ˉ⁵*

-

Spleen

6.6 ± 0.9 x 10ˉ⁶

0.05

Pancreas

2.3 ± 0.8 x 10ˉ⁵

0.16

Brain

1.0 ± 0.6 x 10ˉ⁵

0.07

Heart

5.6 ± 1.9 x 10ˉ⁶

0.04

Skin

1.7 ± 1.3 x 10ˉ⁵*

-

Sum without stomach and intestine

8.0 ± 1.1 x 10ˉ³

-

Total sum

1.4 ± 0.7 x 10ˉ²

98.9

* Tissue weight not known

Applicant's summary and conclusion

Conclusions:

Interpretation of results: absortion in bones was approximately 0.0065% of the amount of substance consumed.Continuous oral intake of radio-labelled HEDP 2-Na led to a small amount of HEDP in the bones. During the test period the amount of HEDP was 0.033% in the total skeleton.; by the end of the test period the proportion was to 0.0065%. It is concluded that a small proportion of HEDP administered in drinking water is absorbed in the intestinal tract and reaches the bones. The amount in the skeleton decreases after administration ceases.

Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.

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